Relationship of Early Changes in Bone Resorption to the Reduction in Fracture Risk With Risedronate

Eastell, Richard; Barton, Ian; Hannon, R.; Chines, Arkadi; Garnero, Patrick; Delmas, P.D.

doi:10.1359/jbmr.2003.18.6.1051

Cited by 549 publications

(338 citation statements)

References 25 publications

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“…Alendronate [10,17,18,19,20,21] Formation: BALP, PINP, PICP, OC Fracture, BMD Resorption: sCTX, uNTX, DPD Risedronate [12,22] Resorption: uDPD, uCTX, uNTX, Fracture, BMD Teriparatide [13,14,15,33] Formation: BALP, PICP, PINP Fracture, BMD Resorption: uDPD, uNTX, sCTX Raloxifene [30,31,32] Formation: BALP, PINP, OC Fracture Resorption: uCTX Early changes in BTM to monitor anti-osteoporosis therapy Similar to most chronic diseases, monitoring the efficacy of treatment of osteoporosis is a challenge. In contrast to BMD, which typically changes in response to therapy less than 2-5% per year, or a maximum of 3% in 3-6 months, most of osteoporosis therapies act by reducing or increasing individual BTM levels or their ratios by 30-200% within 3-6 months.…”

Section: Treatmentmentioning

confidence: 99%

“…The relationships between vertebral fracture risk and changes from baseline in sCTX and uNTX were not linear (p b 0.05). In the original publication [22] below a decrease of 55-60% for sCTX and 35-40% for uNTX, the authors concluded that the decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk but that there was little further improvement in anti-fracture efficacy below a decrease of 55-60% for sCTX and 35-40% for uNTX. [22].…”

Section: Treatmentmentioning

confidence: 99%

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Role of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy

Reginster¹,

Collette²,

Neuprez³

et al. 2008

Bone

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This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. Author's personal copy EditorialRole of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy AbstractMost of the currently available anti-osteoporosis medications promptly and significantly influence the rate of bone turnover. Biochemical markers of bone turnover now provide a high sensitivity to change, allowing the detection of these bone turnover changes within a couple of weeks. Since the anti-fracture efficacy of inhibitors of bone resorption or stimulators of bone formation appears to be largely independent of baseline bone turnover, biochemical markers do not appear to play a significant role in the selection of one particular drug, for an individual patient. However, there are consistent data showing that short-term changes in biochemical markers of bone turnover may be significant predictors of future changes in bone mineral density or fracture reduction, hence suggesting that bone turnover markers play a significant role in the monitoring of anti-osteoporosis therapy. © 2008 Elsevier Inc. All rights reserved.Keywords: Osteoporosis; Monitoring; Treatment; Bone density; Markers of bone turnover IntroductionClinical trials, conducted since the early nineties, have unequivocally shown the ability of several anti-osteoporosis medications to reduce fracture occurrence at various skeletal sites, including but not exhaustively the spine and hip [1]. Whereas the operational definition of osteoporosis is still based on a low bone mineral density (BMD), because low BMD is known to contribute to increased fracture risk, changes in bone mass and density, in response to anti-resorptive therapy, account for only a small portion of the predicted fracture risk reduction [2], a picture which may, however, be significantly changed with the availability of new therapies stimulating bone formation [3] or uncoupling bone formation from bone resorption [4].During the last decade, biochemical markers of bone turnover (BTM) have been developed, that are more sensitive than conventional ones for detecting abnormalities or changes of bone turnover rate [5]. Increased levels of bone resorption, and short-term changes in BTM, have been shown to predict the risk of fracture, independently of the level of BMD in untreated individuals [6,7].Dynamic changes in bone turnover, estimated by measurement of bone biochemical markers, such as breakdown products of type I collagen and proteins secreted by osteoblasts and osteoclasts in blood and urine, can also account for a major portion of antifracture efficacy of anti-resorptive or bone-forming agents [8]. Most of the currently marketed anti-osteoporos...

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Section: Treatmentmentioning

confidence: 99%

Section: Treatmentmentioning

confidence: 99%

Role of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy

Reginster¹,

Collette²,

Neuprez³

et al. 2008

Bone

View full text Add to dashboard Cite

show abstract

“…However, recent findings from a large fracture trial indicate no further anti-fracture benefit with further decreases in bone resorption markers below a decrease of 55% to 60% for uCTx and 35% to 40% for uNTx. 69 Further research is needed to establish the cut-offs of each bone turnover markers based on the probability of fracture in large clinical trials of each therapeutic regimen.…”

Section: Bone Turnover Markersmentioning

confidence: 99%

Canadian Consensus Conference on Osteoporosis, 2006 Update

Brown¹,

Fortier²,

Frame

et al. 2006

Journal of Obstetrics and Gynaecology Canada

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Objective-To provide guidelines for the health care provider on the diagnosis and clinical management of postmenopausal osteoporosis.Outcomes-Strategies for identifying and evaluating high-risk individuals, the use of bone mineral density (BMD) and bone turnover markers in assessing diagnosis and response to management, and recommendations regarding nutrition, physical activity, and the selection of pharmacologic therapy to prevent and manage osteoporosis. Values-The quality of evidence is rated using the criteria described in the report of the Canadian Task Force on the Periodic Health Examination. Recommendations for practice are ranked according to the method described in this report.

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“…(4) The decrease in BTMs has been associated with an improvement in fracture risk resulting from anticatabolic treatment; thus larger decreases in BTMs are associated with greater fracture efficacy. (7)(8)(9)(10) The International Osteoporosis Foundation recommends that bone turnover be used for monitoring the treatment of individual patients with osteoporosis. (11) It is therefore important that we have a complete description of the change in BTMs, especially when the drug belongs to a new class and results in a distinct BTM profile compared with existing therapies.…”

mentioning

confidence: 99%

Effects of denosumab on bone turnover markers in postmenopausal osteoporosis

Eastell

Christiansen

Grauer

et al. 2010

Journal of Bone and Mineral Research

206

115

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Denosumab, a fully human monoclonal antibody to RANKL, decreases bone remodeling, increases bone density, and reduces fracture risk. This study evaluates the time course and determinants of bone turnover marker (BTM) response during denosumab treatment, the percentage of denosumab-treated women with BTMs below the premenopausal reference interval, and the correlations between changes in BTMs and bone mineral density (BMD). The BTM substudy of the Fracture REduction Evaulation of Denosumab in Osteoporosis every 6 Months (FREEDOM) Trial included 160 women randomized to subcutaneous denosumab (60 mg) or placebo injections every 6 months for 3 years. Biochemical markers of bone resorption (serum C-telopeptide of type I collagen [CTX] and tartrateresistant acid phosphatise ) and bone formation (serum procollagen type I N-terminal propeptide [PINP] and bone alkaline phosphatase [BALP]) were measured at baseline and at 1, 6, 12, 24, and 36 months. Decreases in CTX were more rapid and greater than decreases in PINP and BALP. One month after injection, CTX levels in all denosumab-treated subjects decreased to levels below the premenopausal reference interval. CTX values at the end of the dosing period were influenced by baseline CTX values and the dosing interval. The percentage of subjects with CTX below the premenopausal reference interval before each subsequent injection decreased from 79% to 51% during the study. CTX and PINP remained below the premenopausal reference interval at all time points in 46% and 31% denosumab-treated subjects, respectively. With denosumab, but not placebo, there were significant correlations between CTX reduction and BMD increase (r ¼ À0.24 to À0.44). The BTM response pattern with denosumab is unique and should be appreciated by physicians to monitor this treatment effectively. ß

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Relationship of Early Changes in Bone Resorption to the Reduction in Fracture Risk With Risedronate

Cited by 549 publications

References 25 publications

Role of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy

Role of biochemical markers of bone turnover as prognostic indicator of successful osteoporosis therapy

Canadian Consensus Conference on Osteoporosis, 2006 Update

Effects of denosumab on bone turnover markers in postmenopausal osteoporosis

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